A Case Series of Immune Flare and Lupus Anticoagulant Following COVID-19 Vaccination

Background: Vaccination against COVID-19 has garnered concerns for unusual post-vaccination complications. We present 2 cases of immune flare following COVID-19 vaccination.

Case Report: Our first patient was a 53-year-old male who presented with a swollen left leg, hypoxia and palpitations after a trans-Atlantic flight. Chest computed tomography showed bilateral subsegmental pulmonary emboli, with no evidence of right heart strain and Doppler ultrasonography of the lower extremities showed significant clot burden in the left femoral, popliteal, tibial and peroneal veins. Workup revealed thrombocytopenia of 81,000/μL (normal range [NR] 150,000-450,000/μL), elevated D-dimer of 6.25 μg/ml (NR < 0.5 μg/ml), elevated partial thromboplastin time at 94 seconds without heparin. Mixing studies corrected partially to 60.9 seconds (NR 22.5-39.4), indicating the presence of an inhibitor, and lupus anticoagulant was confirmed with dilute Russell viper venom ratio of 3.66 (NR 0.00-1.20) and silica clotting time ratio of 3.95 (NR 0.00-1.22). Anti-beta-2 glycoprotein and anti-cardiolipin antibodies, factor V Leiden mutation, prothrombin G20210A mutation, protein C and protein S were negative. He received 2 doses of the ChAdOx1 nCoV-19 adenoviral vaccine 6 weeks previously. Due to suspicion for vaccine-induced thrombotic thrombocytopenia, enzyme-linked immunoassay for anti-platelet-factor 4 antibody was tested, which was negative. Immediate anticoagulation therapy with low-molecular weight heparin was started and then switched to rivaroxaban.

Our second patient was an 18-year-old male who presented with 2 weeks of right-sided lower chest pain. The cardiopulmonary workup was negative, with a computed tomography of the chest showing a borderline enlarged spleen at 13 cm, and hepatic steatosis. He was taking indomethacin for slipped rib pain and was less mobile than usual. One week later, he developed left posterior thigh pain extending down the posterior calf and was found to have totally occluding left leg deep venous thrombosis from femoral vein mid to distal, popliteal, posterior tibial, peroneal, gastrocnemius and soleal veins. Workup was significant for prolonged partial thromboplastin time at 78 seconds, which partially corrected to 62 seconds with mixing studies, elevated C-reactive protein of 5.4, positive antinuclear antibodies (1:1280), normal complement (C3 and C4) and negative RF, SS A/Ro, SS B/La, RNP, smooth muscle, LKM antibodies. He started anticoagulation with low-molecular weight heparin, which was transitioned to apixaban. His family history was significant for lupus in his aunt and grandmother; however, there was no family history of thrombosis. He had received the third mRNA COVID vaccine 2 weeks prior to presentation. Additional workup revealed positive lupus anticoagulant, beta-2 glycoprotein, cardiolipin antibodies, and he was started on warfarin with a target international normalized ratio of 2-3 and repeat testing 3 months later revealed persistent elevation, indicating antiphospholipid syndrome. Although there was low suspicion for vaccine induced thrombotic thrombocytopenia, heparin-induced thrombocytopenia panel was performed and was negative.

Discussion: Multiple SARS-CoV-2 vaccines were rapidly developed and approved, but long-term effects are unknown. Recombinant adenoviral vector-based vaccines raised concerns for an unusual post-vaccination coagulopathic syndrome with anti-platelet-factor 4 antibodies seen in 90% of probable and definite cases of vaccine-induced thrombotic thrombocytopenia (Pavord et al). Positive lupus anticoagulant has been noted with severe COVID-19 (Tung et al); however, our first patient had no history of COVID-19. This presentation was attributed at the time to a pro-inflammatory state induced by vaccination that may have caused lupus anticoagulant titers to rise leading to thrombosis as seen in this case. Autoimmune manifestations after COVID-19 vaccination are thought to be due to molecular mimicry, autoantibodies, vaccine adjuvants and a pro-inflammatory cascade among multiple other mechanisms (Chen et al). Similar to other viral infections, COVID-19 and additionally vaccination against it may lead to flare of immune mediated diseases (Talotta et al) as what occurred in our second patient with predisposition to hypercoagulable state given his family history of systemic lupus erythematosus.

No relevant conflicts of interest to declare.